Phase 3a Mike Tonkins€¦ · Disorders of… –Movement –The neuromuscular junction –Muscle...

Phase 3a

Mike Tonkins

The Peer Teaching Society is not liable for false or misleading information…

Disorders of…

– Movement

– The neuromuscular junction

– Muscle

– Spinal cord

– Cranial and peripheral nerve palsies

…plus dermatomes and myotomes.


Aims

• Diagrams to illustrate breadth of an area

• Cases and questions to highlight most important pathologies

• Notes (where practicable) on other conditions


Introduction

GB, a 68-year-old gentleman, presents to his GP with “clumsiness”. He’s been having problems for about 6 months - he noticed it initially when his hobby, building model ships, became harder to do. He feels this has been getting worse. His wife has pointed out that he gets a “twitch” whilst watching TV, and she thinks he looks different – a bit like he’s always staring at her. Diagnosis?


Case 1


Movement Disorders Neurological conditions that affect the speed,

fluency, quality and ease of movement

Glossary:

• Hypokinesia, hyperkinesia

• Dyskinesia

• Bradykinesia

• Hypotonia, hypertonia

• Tremor

• Chorea, athetosis, choreo-athetosis

• Hemiballismus

• Dystonia

• Tics

• Myoclonus


Causes of Parkinsonism

1. What is parkinsonism?

2. What is Parkinson’s Disease?

3. How might each of the core features present?

4. List five non-motor features.

5. Name three classes of pharmacological therapy.


Parkinson’s Disease

1. Parkinsonism is the classical triad of tremor, rigidity and bradykinesia 2. Parkinson’s disease is a syndrome of tremor, rigidity and bradykinesia due to the loss of dopaminergic neurons of the substantia nigra 3. Bradykinesia

– Poverty/slowing of movement • Fatiguing, decremental

– Difficulty in initiating movement • Micrographia, difficulty doing buttons, zips

– Facial immobility • Mask-like semblance, serpentine stare

• Tremor – A resting tremor of 3-6 Hz, described as pill rolling – Usually 1 upper limb initially; spreads to same side leg then opposite side – Reduced when that limb is in motion

• Rigidity – Lead pipe (plastic) rigidity all range of movement is affected equally – Cogwheel rigidity when tremor is present

4. Non-motor symptoms

– Anosmia (90%)

– Depression/anxiety (50%)

– Dementia

– Dribbling saliva

– Postural instability

– REM sleep behaviour disorder

– Autonomic features (Urinary urgency, Hypotension)

– Constipation

– Seborrhoea 5. See slide 10.





Direct: neurons from the pars

compacta facilitate stimulation of

inhibitory neurons in the putamen,

thereby releasing thalamic inhibition

Indirect: neurons from the pars

compacta inhibit putamen-globus

projection, in order to prevent

inhibition of the thalamus


Parkinson’s Disease Loss of dopaminergic neurons in the pars compacta of the substantia nigra, locus ceruleus and other

locations

Dopamine:

Excitatory influence upon direct striatal pathway

Inhibitory influence upon indirect striatal pathway

Therefore ↓ dopamine leads to:

Underactivity of direct pathway

The internal pallidum and pars reticularis are disinhibited

Therefore the thalamus is inhibited

Overactivity of indirect pathway

Inhibition of external pallidus is easier

Subsequent disinhibition of subthalamic nuclus

So excessive excitation of internal pallidu and pars reticulata

Therefore the thalamus is inhibited

Both changes exascerbate overactivity of (inhibitory) internal pallidal output cells, producing akinesia

Compensation

Up to 70% of dopaminergic neurons can be lost before symptoms appear

Partly due to increased production of DA by remaining neurons

Partly due to up-regulation of DA receptors


Parkinson’s Plus

What about if this patient also had…

1. …a symmetrical onset tremor and truncal rigidity?

2. …orthostatic hypotension and bladder disturbance?

3. …visual hallucinations, and was kicking his wife out of bed?


Parkinson’s Plus Neurodegenerative diseases featuring classical features of Parkinson's disease with additional features

that distinguish them from idiopathic Parkinson's.

Progressive supranuclear palsy

A tauopathy: neurofibrillary tangles of tau protein

Parkinsonism + postural instability and falls, + vertical gaze palsy, + symmetrical onset, + truncal rigidity

Corticobasal degeneration

A tauopathy: neurofibrillary tangles of tau protein

Parkinsonism

+ apraxia,+ aphasia ,+ asterognosis

Multiple system atrophy, aka Shy-Drager Syndrome

Cell loss with subsequent gliosis

Parkinsonism, + autonomic dysfunction (postural hypotension, bladder dysfunction), + cerebellar signs

Dementia with Lewy Bodies

Lewy bodies are alpha-synucelin and ubiquitin

Parkinsonism + Variation in cognition + Visual hallucinations + REM sleep disturbance + Orthostatic

hypotension


Causes of Hyperkinesis


Huntington’s Disease

The dopaminergic neurons (blue) are stimulating the excitatory direct pathway, and

depressing the inhibitory indirect pathway, resulting in uncontrolled movements


Huntington’s Disease Aetiology

Autosomal dominant condition

Genetics

Triplet repeat on the Huntingtin gene; up to 35 is normal, but more are pathological

Most patients have 40-50 repeats; presents 30-50 years

>40 repeats lowers age of onset to 15-30 years

Increased number of repeats correlates with increased severity

Fully penetrant

Pathogenesis

Attrition of cells that project to external globus pallidus from putamen

This results in a relative excess of dopamine

The dopamine has different effects on the different pathways

Acts as an accelerator in the direct pathway: resulting in too much movement

Excessive inhibition of the indirect pathway, which leads to it not playing its full inhibitory function

History & examination

Chorea (basal ganglia)

Dementia/psychiatric disorder (frontal cortex)

Personality changes (frontal cortex)

Management

Phenothiazines

e.g. Chlorpromazine

The D2 antagonism may help control movements

SSRIs

May help mood disturbance

FL, a 38-year-old female presents to her GP complaining of problems swallowing. She’s noticed that it tends to be worse towards the end of the meal. She also complains that she’s been feeling weak recently, especially around her shoulders. She is flushed and tachycardic, with a slight tremor in her hands. She has a slight asymmetrical ptosis, and normal reflexes. Diagnosis?


Case 2


The Neuromuscular Junction

1. Define myasthenia gravis

2. Name two examination techniques you could use to elicit muscle fatiguability

3. Explain the examination findings.

4. Why would you order a CXR as a first-line investigation?

5. What diagnostic tests could you do?

6. Name four management options.


Myasthenia Gravis

1. An auto-immune disease in which there is destruction of nicotinic acetylcholine receptors

2. Peek test, myasthenic snarl, counting to 50

3. Weakness due to MG. Other Sx due to hyperthyroidism (present in 15%). Other autoimmune diseases are closely associated with MG, e.g. RA, SLE, hypothyroidism,

4. About 75% have thymic abnormalities – usually hyperplasia (~70%) occasionally thymoma (~10%)

5. Ice test. Tensilon test. Serum auto-antibodies (anti-AChR, Anti-MSK)

6. Anticholinesterases (pyridostigmine), immunosuppressants (prednisolone), thymectomy (improves prognosis), plasmapheresis (if very sick), IV immunoglobulin (during exacerbation)


Myasthenia Gravis

• Lambert-Eaton Myasthenic Syndrome is an autoimmune disorder in which the function of pre-synaptic voltage-gated Ca2+ channels is impaired by autoantibodies, resulting in impaired ACh release.


MG vs LEMS

MG LEMS

Distribution Cranio-bulbar prominent Largely truncal

Fluctuation Worse after exertion Improves after exertion

Somatic vs Autonomic Somatic Somatic + autonomic

Reflexes Present, fatigue Absent, restore

Tensilon test Positive Negative

Antibodies Anti-nAChR (80-90%) Anti-MSK

Anti-VGCC (75-100%)

Associations Thymic (75%), autoimmune Cancer (40%), most SCLC

• A 58-year-old solicitor presents to his GP with back pain. The pain came on three days ago when he was gardening and stood up carrying a bucket of soil. Since then he’s started getting shooting pains down the back of his calf. On examination there is weakness of ankle plantarflexion and a reduced ankle reflex. Diagnosis?


Case 3


Cord (& Nerve Root) Pathology

Mechanical Infection/Inflammation Neurological

Disc prolapse Spondlyoarthropathies Spinal stroke

Spondylolisthesis Connective tissue diseases Acute transverse myelitis

Canal stenosis Discitis Subacute combined degeneration of the cord

Tumours Spinal TB Motor neurone disease

Fracture Hereditary spastic paraparesis

Paget’s Syringomyelia

Tabes dorsalis

1. Which disk is likely to have prolapsed?

2. Is it likely to be a lateral or a posterior prolapse?

3. List 5 red flags that you would elicit in your history and examination

4. List 4 LMN and 4 UMN signs.

5. What neurological signs might you expect to see if the prolapse occurred in the C5 nerve root?


Lumbar Radiculopathy

1. The L5/S1 disk, impinging the S1 nerve root

2. A lateral prolapse. Posterior would cause cauda equina syndrome

3. Saddle parasthesia, sphincter disturbance, reduced anal tone, lower limb paralysis, lower limb parasthesia

4. LMN: wasting, fasciculations, hypotonia, reduced reflexes

UMN: hypertonia (spasticity), increased reflexes, pronator drift, Babinski sign

5. LMN signs at the level of the lesion

T normal P weak deltoid S ↓deltoid C normal R ↓biceps +/- ↓suppinator


Lumbar Radiculopathy


Some points to note

• It’s not enough just to know the dermatomes: it is also important to know which nerve the fibres travel with (i.e. the innervation)

– E.g. pain in lateral 3.5 digits due to median nerve compression spans C6 & C7 dermatomes

• Myotomes are tested by selected joint movements – there’s no myotome equivalent of the dermatome map.


Dermatomes - limbs


Innervation


Dermatomes - trunk


Myotomes - Arm


Myotomes - Leg Toe adduction

S2, S3

Hip flexion

Knee extension

Knee flexion

plantarflexion

An 18-year-old fresher attends the emergency department in early October. She’s had some tingling in her hands and feet for a week, and since yesterday has been feeling “tired”…but this morning her legs were so weak she could hardly stand. On examination she is areflexic in the lower limb and has symmetrical loss of light touch sensation to the knee. Diagnosis?


Case 4

Nerve Palsies

Cranial

III, IV, VI V VII IX, X, VI, XII

Peripheral

Mononeuro-pathies

Mono-neuritis

multiplex

Polyneuro-pathy

• From Latin paralysis meaning…paralysis


Nerve ‘Palsies’

So we’re only looking at conditions in which loss of motor function is prominent.

Important omissions are MS, MND and autonomic neuropathy which are topics in

their own right.

1. Define Gullain-Barré syndrome.

2. Name two non-motor, non-sensory symptoms.

3. What parameter would you monitor closely on this patient?

4. Name two potential treatments.

5. How would you differentiate a case of GBS from myasthenia gravis?


Gullain-Barré Syndrome

1. Acute, autoimmune, demyelinating polyneuropathy

2. Back pain, due to weakening of muscles. Autonomic symptoms, e.g. tachycardia

3. Her peak expiratory flow rate – 20% of patients need ventilation for type 2 respiratory failure

4. IV immunoglobulin and plasmapheresis

5. In myasthenia gravis there are no sensory symptoms, weakness starts proximally*, tendon reflexes are preserved.

*Although there is a variant of GBS called miller-fisher syndrome in which ocular palsy is prominent; however this occurs with ataxia thus distinguishing it from MG.


Gullain-Barré Syndrome

Inflammatory Genetic Metabolic Other

GBS Charcot-Marie-Tooth Diabetes mellitus Paraproteinaemic

Chronic inflammatory demyelinating polyradiculopathy

Uraemia Paraneoplastic

Multifocal motor neuropathy with conduction block

Hyperthyroidism Vasculitidies

Alcohol

B vitamin deficiency


Polyneuropathies


Mononeuropathies

• Spot diagnosis…

1

2

3

4

1. Median nerve – carpal tunnel syndrome

2. Ulnar nerve – cubital tunnel syndrome or guyon’s canal syndrome

3. Radial nerve – honeymoon palsy

4. Common peroneal nerve – foot drop


Mononeuropathies

• Sequential or simulataneous palsy of several nerves

• Associated with various diseases

– Diabetes

– Vasculitidies

– Malignancy (paraneoplastic)

– HIV


Mononeuritis Multiplex


Cranial Nerve Palsies

Get to know and understand pupil abnormalities, e.g. innervation,

meiosis and mydriasis, holmes-aidie pupil, argyll-roberts pupil, relative

afferent pupillary defect. It really is worth the time and you’ll pick up lots

along the way.



A B

C D E

A. Right CN VI.

– Failure to abduct eye with lateral rectus

B. Right CN IV.

– Failure to depress, rotate & adduct eye with superior oblique

C. Right CN V.

– Trigeminal nerve supplies motor innervation to pterygoids (open), temporalis & masseter (close)

– Remember: pTerygoids and Tongue go Towards the lesion

D. Left CN III. Partial palsy

– Ptosis (failure of levator palpebrae superioris)

– Depression (unopposed sup oblique, CN IV)

– Abduction (unopposed lateral rectus, CN VI)

– NB: pupil reactive (same size as other pupil). If dilated & unreactive it would be a complete palsy

E. Left CN VII. Bell’s palsy

– The forehead is affected, indicating this is a LMN lesion.

– In UMN lesions the forehead is spared due to bicortical innervation.




“Explain Bell’s Palsy again…” Upper motor neurons project from

the motor cortex to both facial

nerve nuceli. This is bicortical

innervation

These UMNs just so happen to

be the ones that innervate the

forehead.

From the facial nerve nuceli, the

lower motor neurons only

innervate one side of the face

Therefore a LMN lesion affects

the whole face. However an

UMN lesion spares the forehead

because the fibres from the other

cortex conduct to the LMNs.

• Bulbar palsy refers to lower cranial nerve lesions (IX, X, XI, XII)

• The ‘bulb’ is the medulla; these nerves all have their nuclei close together there

• True bulbar palsy is of the cranial nerves or nuceli – i.e. lower motor neurone

• Pseudobulbar palsy is of the corticobulbar fibres – upper motor neurone


A word on bulbar palsies…


Some more on bulbar palsies…

Disorders of…

– Movement

– The neuromuscular junction

– Muscle

– Spinal cord

– Cranial and peripheral nerve palsies

…plus dermatomes and myotomes.


Aims Mechanical Infection/Inflammation Neurological

Disc prolapse Spondlyoarthropathies Spinal stroke

Spondylolisthesis Connective tissue diseases Acute transverse myelitis

Canal stenosis Discitis Subacute combined degeneration of the cord

Tumours Spinal TB Motor neurone disease

Fracture Hereditary spastic paraparesis

Paget’s Syringomyelia

Tabes dorsalis

Nerve Palsies

Cranial

III, IV, VI V VII IX, X, VI, XII

Peripheral

Mononeuro-pathies

Mono-neuritis

multiplex

Polyneuro-pathy

Thanks!


Phase 3a Mike Tonkins€¦ · Disorders of… –Movement –The neuromuscular junction –Muscle...

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